The overall objectives of this research are to study mood disorders following focal brain injury using clinical examination and imaging techniques and to study the mechanisms of lateralized behavioral response to focal brain injury in rats. During the ten years of support (RSDA I and II), we have found that major depressive disorder following stroke occurs in approximately 25% of stroke patients and is significantly associated with left frontal cortical and left basal ganglia lesions. The current application proposes to extend this work by examining patients with specific mental phenomenon which may interfere with the expression or diagnosis of depressive disorder. Specifically, we will examine the frequency and clinical manifestations of depression in patients with and without aprosody (the inability to either comprehend or express emotion), neglect (visual, auditory or tactile neglect), anosagnosia (denial of motor impairment) or emotional lability (laughter or crying without an underlying consistent emotion). These clinical findings will be correlated with findings from structural imaging using MRI scans and functional imaging using PET scans to examine questions of how these mental phenomenon may interact with the expression of a mood disorder, whether depression leads to specific focal changes in serotonin receptors or regional brain metabolic rates, and whether the treatment of depression leads to specific changes in associated clinical phenomenon or functional brain imaging. The final section of work will involve the determination of factors which influence the development of a lateralized behavioral response to brain injury in the rat. This laboratory work may shed light on the developmental process of cerebral lateralization which may in turn lead to the identification of a substrate for the lateralized expression of mood disorders following brain injury in humans. Collaborative efforts engendered by this work in neuropsychiatry and behavioral neuroscience, will form a basis for continued professional growth and increased interdisciplinary interaction.